The Tumor Biology and Microenvironment (TBM) Program aims to eradicate cancer by identifying the cellular and molecular mechanisms that drive interactions between tumors and their microenvironments, and develop and test innovative diagnostic and treatment strategies. This highly integrated program includes 36 members from 16 WSU departments and $14,193,608 in grants, of which $5,908,215 is peer reviewed. The Program goals are addressed with three themes that encompass basic, preclinical, and clinical research. The first theme identifies and exploits the mechanisms that confer phenotypical plasticity and survival of tumor cells in tumor progression. Translational research is conducted to evaluate the potential clinical application of these molecular determinants as tumor markers and/or therapeutic targets. The second theme identifies and exploits the mechanisms that confer the unhealable wounding of tumor stroma. Our investigators identify and characterize factors in an extracellular proteolysis and signaling network that enable tumor cells to adapt to and subvert the microenvironment in the development of bone metastases. Key molecules in this network are evaluated to determine if they can be used to predict cancer progression and treatment outcomes. The third theme identifies and exploits the host immune response to tumor progression. Bispecific antibody-armed activated T-cells are tested in solid tumors and hematologic malignancies in the context of chemotherapy or high dose chemotherapy and stem cell transplantation. Anti-tumor DNA vaccines are developed and tested using mouse and domesticated cat models. Our investigators study immune modulators and inhibitors of adverse pro-inflammatory responses. Our members also develop novel vehicles to deliver immunotherapeutic agents. TBM Program members actively collaborate with members of the MI, MT, and PSDR Programs at KCI. Of the 612 manuscripts published from December 2010 to November 2014, 44% and 38% were intra- and inter-programmatic, respectively, and 27% were multi-institutional collaborations.